The overall theme of our program is to understand the signals that cause and that regulate malignant lymphomas. Our focus is on the immune system, since these tumors are derived from the cells of the immune system. We plan to extend findings made in our current program and to take advantage of new technology that we have helped develop. To enable our work we have access to large numbers of patients with lymphoma, and we have built a tumor tissue bank and clinical database extending over several decades. Specific Projects: 1.We are developing a new strategy for inducing an immune response against lymphoma. Immune signaling molecules are injected directly into the tumor at one site in conjunction with the induction of apoptosis/necrosis at that same site. We will conduct a prototype clinical trial and test preclinical animal models 2. Our goal is to discover the signal transduction pathways that govern clinical behavior of lymphomas. A new method of flow cytometry for intracellular signaling pathways will be used on lymphoma specimens. Differences between tumors will be related to clinical outcome. The signaling relationships between tumor and host immune cells will be interrogated and new targets will be sought. 3. A transgenic mouse develops lymphoma as a result of an activated MYC gene. These lymphomas regress when the MYC gene is turned off, but only when the host has an intact immune system. We will determine whether this control is due to an immune response or to signals that regulate lymphoid homeostasis.